The Axel Laboratory

We are also committed to using the power of molecular biology to perturb the mouse olfactory system as a means of elucidating sensory coding. We have generated a mouse with a ‘‘monoclonal nose’’ in which greater than 95% of the sensory neurons express a single odorant receptor, M71. As a consequence, the frequency of sensory neurons expressing endogenous receptor genes is reduced 20-fold. We observe that these mice can smell, but odor discrimination and performance in associative olfactory learning tasks are impaired. However, these mice cannot detect the M71 ligand acetophenone despite the observation that virtually all sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice readily detect other odors in the presence of acetophenone. These observations have implications for how receptor activation in the periphery is represented in the brain and how these representations encode odors.

The early olfactory system of the fruit fly is remarkably similar to that of the mouse. As with the mouse, we continue a long-term project of genetically and physiologically dissecting the sensory coding of odors in the fly. In addition, we are pursuing odor-responsive networks further into the fly brain to discover the pathways by which sensory responses are converted into behavior. Flies, like other animals, exhibit a repertoire of innate behaviors that result in stereotyped social and sexual responses to the environment. In Drosophila, courtship behaviors governed by pheromonal excitation of peripheral olfactory pathways ultimately activate behavioral circuits in higher brain centers. One pheromone, cVA, elaborated by the male, suppresses male-male courtship but in females, enhances receptivity to courting males. Thus, a single pheromone elicits different behaviors in the two sexes. We have developed a neural tracing procedure that employs two-photon laser scanning microscopy to activate the photoconvertible fluorophore, PA-GFP, to demonstrate anatomic dimorphisms in the neural circuit responsive to the pheromone cVA. The observation that cVA activates a sexually dimorphic circuit in higher olfactory centers suggests a mechanism whereby a single pheromone can elicit different behaviors in males and females.